The cyclisation of acyclic isoprenoid compounds is a very powerful and effective cascade reaction because it can construct multiple rings in a single one step reaction. The reaction has therefore been a focus in the construction of polycyclic molecules due to its efficiency of C—C bond formation and stereospecificity. This contributes to increasing product yield, reducing processing time as well as waste production. Processes known in the art use various types of catalysts for the cyclisation reaction. A commonly used type of catalyst are Lewis acids. Using chiral Lewis acids terpene rings could be constructed asymmetrically.
The intramolecular acetal-initiated cationic isoprenoid cyclisation reaction was first introduced by W. S. Johnson (e.g. Johnson, W. S., & Kinnel, R. B., J. Am. Chem. Soc. (1966) 88, 3861-3862; Johnson, W. S., Angew. Chem., Int. Ed. (1976) 15, 9-16; Johnson, W. S., Acc. Chem. Res. (1968) 1, 1-8.). Since then, this method has been extensively developed to afford bicyclic, tricyclic, tetracyclic and even pentacyclic products in respectable to good yields. Asymmetric induction has also been achieved using chiral acetal templates, providing enantiomeric excess of up to 90%. However, there exist some disadvantages in using acetals for intramolecular polyene cyclisations. The need to incorporate the required acetal into the acyclic precursor introduces added synthetic complexity. In addition, the accommodation of the acetal moiety also diminishes the structural flexibility in the acyclic precursor. These two problems can reduce the scope and applicability of the method substantially.
It is therefore an object of the present invention to overcome these problems and to provide a new method of preparing a multiple ring compound.